In the seventies non specific immunotherapy with B.C.G. was used for a number of malignancies in man. After initial successful reports on leukaemia and melanoma, results could not always be confirmed and the use of B.C.G. seemed to be limited. In 1976 B.C.G. was used for the first time intravesically in patients with superficial bladder cancer. At present non specific immunotherapy with B.C.G. for superficial bladder cancer is considered the most efficacious treatment modality. It is probably the most widely used and most successful immunotherapy in man. A number of issues on this treatment are still unclear. No consensus has been reached about the treatment schedule, optimal dose and appropriate BCG strain while toxicity is more pronounced than in intravesical chemotherapy. Improvement of the treatment as well as basic research are necessary and will determine the exact place of B.C.G. in the coming years.
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Therapies against hematological malignancies using chimeric antigen receptors (CAR)-T cells have shown great potential; however, therapeutic success in solid tumors has been constrained due to limited tumor trafficking and infiltration, as well as the scarcity of cancer-specific solid tumor antigens. Therefore, the enrichment of tumor-antigen specific CAR-T cells in the desired region is critical for improving therapy efficacy and reducing systemic on-target/off-tumor side effects. Here, we functionalized human CAR-T cells with superparamagnetic iron oxide nanoparticles (SPIONs), making them magnetically controllable for site-directed targeting.
View Article and Find Full Text PDFBackground: -related schwannomatosis ( -SWN) is a debilitating condition that calls for robust treatment options. The defining feature of -SWN is the presence of bilateral vestibular schwannomas (VSs), which grow over time and can result in irreversible sensorineural hearing loss, significantly affecting the quality of life for those affected. At present, there are no FDA-approved medications specifically for treating VS or related hearing loss.
View Article and Find Full Text PDFT cell receptor (TCR) mimics offer a promising platform for tumor-specific targeting of peptide-MHC in cancer immunotherapy. Here, we designed a α-helical TCR mimic (TCRm) specific for the NY-ESO-1 peptide presented by HLA-A 02, achieving high on-target specificity with nanomolar affinity (K = 9.5 nM).
View Article and Find Full Text PDFTertiary lymphoid structures (TLS) are organized immune cell aggregates that arise in chronic inflammatory conditions. In cancer, TLS are associated with better prognosis and enhanced response to immunotherapy, making these structures attractive therapeutic targets. However, the mechanisms regulating TLS formation and maintenance in cancer are incompletely understood.
View Article and Find Full Text PDFFront Immunol
December 2024
Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, United States.
Background: Microsatellite instability-high (MSI-high) tumors comprise ~15% of sporadic colorectal cancers (CRC) and are associated with elevated T cell infiltration. However, the universality of this response across T cell subtypes with distinct functions is unknown.
Methods: Including 1,236 CRC tumors from three observational studies, we conducted T cell profiling using a customized 9-plex (CD3, CD4, CD8, CD45RA, CD45RO, FOXP3, KRT, MKI67, and DAPI) multispectral immunofluorescence assay.
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